The human skin consists of two major layers, the bottom thicker layer, dermis and the top thinner layer, the epidermis. Dermis is the layer which provides the strength, elasticity and the thickness to the skin. With aging, the thickness of the dermal layer is reduced and this is believed to be partially responsible for the formation of wrinkles in aging skin. The top layer of human skin or the epidermis which provides the resilience and the barrier properties of the skin, is composed of many different cell types. Keratinocytes are the major cell type of the epidermis (75-80% of the total number of cells in the human epidermis). Within the epidermis the keratinocytes reside in four distinct stages of differentiation. Epidermal differentiation is important for providing the essential function of the skin, namely to provide a protective barrier against the outside environment and to prevent loss of water from the body. Formation of the cornified envelope is the final stage of keratinocyte differentiation. The enzyme responsible for the formation of cornified envelopes, transglutaminase, is a marker of epidermal differentiation.
Another factor, in addition to skin thickness, imparts the barrier function to the skin. Layers of lipids in the skin form a "water barrier" which prevents water loss from the skin, and, consequently, the appearance of aged, dry or wrinkled skin. These lipids consist predominantly of ceramides, cholesterol, and fatty acids. In normal skin, if the barrier function is perturbed, the epidermis re-synthesizes the deficient lipids. Under certain conditions, however, a reduced capacity for re-synthesis may occur. This is especially so with aging or dry skin, where skin lipid levels are in any case sub-normal.
Agents which increase the thickness of the dermal layer and increase the lipid levels in the epidermal layer should therefore be ideal compounds for providing skin conditioning and anti-aging benefits.
In addition, sebum secretion decreases in post-menopausal women. Hormone replacement therapy elevates it toward pre-menopausal levels. Reduced sebum secretion in post-menopausal women may be associated with the skin dryness commonly noted in this group. Any material which enhances sebum production may provide a benefit to these women.
The present invention is based at least in part on the discoveries that the exposure of cultured keratinocytes to 4-chromanone results in the enhancement of differentiation and the expression of lipids essential to barrier function. 4-chromanone was also able to elevate sebum production in human sebocytes.
4-chromanone is a synthetic material, which is used as a starting material in syntheses of biologically active compounds. U.S. Pat. No. 3,864,484 (Madaus) mentions polyhydroxyphenyl chromanones for use in therapeutic compositions to protect from liver damage and inflammation. U.S. Pat. No. 4,065,574 (Moon et al.) mentions the use of 4-chromanone as a starting material for antifungal compounds but application to human skin is not disclosed. Japanese patent application 55111410 discloses the use of 3-Hydroxy-chromanone for skin lightening and sunburn prevention. 3-Hydroxy-chromanone is a tyrosinase inhibitor and uses 4-chromanone as a synthetic starting material.